Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Earlier, we reported that prophylactic treatment with human interferon gamma (rHuIFN-gamma) protected monkeys against Plasmodium cynomolgi B malaria infection. We have tested the efficacy of rHuIFN-gamma on relapsing stage of experimental P. cynomolgi B malaria infection in rhesus monkeys. No effect of rHuIFN-gamma was seen against experimental relapsing stage compared with controls; however, it appears that chloroquine (CHL) may have interfered with the antimalarial effect of IFN, since treatment with CHL inhibits the antiviral activity of mouse alpha/beta IFN and polyinosinic-polycytidylic acid (poly I:C) against Semliki forest virus (SFV) in mice. These results may have clinical implications especially with the use of IFN against virus infection, cancer and in parasitic infections in malaria endemic areas where CHL is one of the most widely used antimalarial drugs. Our result also shows that CHL treatment enhances the virus replication in mice and suggest a possible connection between AIDS and malaria infection, since the spread of AIDS has been rapid in parts of tropical Africa that have a high incidence of malaria, and chloroquine has been frequently used in the chemotherapy of malaria.
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PMID:Effects of interferon in malaria infection. 212 28

Burkitt's lymphoma is the most common childhood cancer in Africa. Most prevalent in areas endemic for malaria, the disease, a malignant growth of lymphoid tissue, usually presents itself as a large tumour of the jaw. When first characterized in the 1950s, the lymphoma was thought to spread by some infectious agent. Subsequent research indicates that the frequent involvement of an infectious agent is but one factor in a more complex aetiology. Today, Burkitt's lymphoma is considered an example of multistep carcinogenesis. Each step in the process results from a different agent. The agent in the first step is the Epstein-Barr virus, which infects B cells of the immune system causing a proliferation of these cells. The second step, malarial infection, furthers the proliferation of B cells providing a large population of cells available for a chromosomal translocation which represents the third step in the formation of the lymphoma. The chromosomal translocation places a cancer causing gene, c-myc, in close proximity to an active antibody-encoding its proliferation resulting in a cell capable of unlimited growth which serves as the nucleus of a B cell lymphoma.
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PMID:Burkitt's lymphoma and the role of Epstein-Barr virus. 216 60

Epstein-Barr virus and HTLV-1 are both lymphotropic viruses, capable of immortalizing lymphocytes in vitro (Fig. 1). Both viruses have been sequenced and subjected to intense molecular biologic scrutiny, and in both cases genes believed to be important in lymphocyte immortalization have been identified. These viral genes are not homologues of cellular oncogenes, nor is there any evidence to suggest insertional mutagenesis. Rather, these genes alter the expression of a variety of cellular genes and, in so doing, alter the growth characteristics of the host cell. Infection with either virus is most likely to be asymptomatic, associated with a benign self-limited lymphoproliferation, or both, but in a small fraction of instances these benign lymphoproliferations give rise to a lymphoma or leukemia. In the case of the Epstein-Barr virus, a variety of cofactors have been identified that are important to the evolution of malignancy. These cofactors include immunosuppression in transplant recipients, cogenital immunodeficiency in the X-linked lymphoproliferative syndrome, human immunodeficiency virus infection in AIDS patients, and malaria in patients with endemic Burkitt's lymphoma. In the case of HTLV-1, cofactors have not been identified. Nonetheless, the importance of cofactors is suggested by the small fraction of the population infected by the virus who actually develop lymphoproliferative disease, and the long latency period between infection and the development of frank lymphoproliferative disease. In organ transplant recipients with lymphomas associated with Epstein-Barr virus infection, the EBV immortalizing/transforming genes are expressed in the malignant tissue. But in Burkitt's lymphoma and in adult T-cell leukemia/lymphoma, the EBV and HTLV-1 immortalizing/transforming genes are not detectably expressed. In Burkitt's lymphoma, it is suggested that the dysregulated myc gene renders the growth effects of Epstein-Barr virus latency genes superfluous. No comparable proto-oncogene translocation or activation has yet been identified in HTLV-1 lymphoma/leukemia.
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PMID:Human lymphotropic viruses associated with lymphoid malignancy: Epstein-Barr and HTLV-1. 217 3

The esters of cephalotaxine-harringtonine, homoharringtonine and deoxyharringtonine--have been reported by both Chinese and American oncologists as useful in the treatment of human nonlymphoblastic leukaemias and selected solid tumours of the head and neck. We report our results with homoharringtonine, currently a Phase II clinical trial drug with the National Cancer Institute, in the treatment of malaria. Homoharringtonine, 2.7-3.4 nM, was effective in causing 50% growth inhibition of two strains of chloroquine-resistant Plasmodium falciparum malaria in vitro. In vivo tests in mice infected with P. yoelii showed that this drug was effective in inhibiting parasite growth in this system as well. Histologically, the drug was associated with karyorrhexis. Drug-exposed cells showed decreased levels of putrescine and spermidine and increased spermine levels. Our findings not only demonstrate the potential usefulness of homoharringtonine in the treatment of chloroquine-resistant malaria, but also demonstrate the advantage of applying comparative biochemistry and an understanding of biological mechanisms in a rational approach to the development and treatment of diseases including malaria.
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PMID:Treatment of chloroquine-resistant malaria with esters of cephalotaxine: homoharringtonine. 222 25

Biopsies of malignant lymphomas collected from all districts of Uganda, filed in the Kampala Cancer Registry for the 8-year period 1966-1973, were reviewed. This review confirmed a relatively low frequency of follicle-centre-cell lymphomas with a follicular growth pattern and the geographical co-distribution between malaria and Burkitt's lymphoma (BL). It also showed a similar, though less marked, association between non-Burkitt, non-Hodgkin's lymphoma (NBNHL) and malarial endemicity, and a correlation in the regional incidence between BL and NBNHL. In both comparisons, these associations were strong for high-grade lymphomas and weak for low-grade neoplasms. BL and other NHL may therefore share, to a varying degree, some common pathogenesis. The excess in frequency of NBNHL of high-grade malignancy in malarial endemic areas appears to be in contrast to Western countries where most non-Hodgkin's lymphomas are of low-grade malignancy.
Int J Cancer 1990 Apr 15
PMID:The distribution of non-Burkitt, non-Hodgkin's lymphomas in Uganda in relation to malarial endemicity. 232 41

In response to malaria infection, phagocytes, such as macro-phages and neutrophils, produce superoxide and thence the other reactive oxygen species (ROS) with which to kill the parasites. Excess ROS is normally eliminated by the body's natural scavenger molecules; however, in the event of a vast excess of ROS, as may be the case in acute as well as chronic malaria patients, the natural scavengers may be overwhelmed. We hypothesize that unscavenged ROS in malaria patients causes DNA damage in normal host cells which, if unrepaired or incorrectly repaired, could result in oncogene activation and eventually lead to cancer. An epidemiologic study may be warranted in malaria-endemic regions to investigate the possible relationship between malaria infection and cancer risk.
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PMID:Reactive oxygen production against malaria--a potential cancer risk factor. 237 89

Mononuclear cells (MNC) isolated from malaria immune donors and from donors never exposed to malaria were stimulated in vitro with soluble purified Plasmodium falciparum antigens (SPag) or PPD. After 7 days of culture the proliferative response and the cytotoxic activity against the natural killer cell (NK cell) sensitive cell line, K562, were measured. It was found that SPag stimulation enhanced cytotoxic activity of MNC from donors whose lymphocytes exhibited a strong proliferative response to the antigen. MNC with low proliferative responsiveness showed increased cytotoxic activity if the MNC were preincubated with interleukin 2 (IL-2) for one hour before the start of the cytotoxic assay. SPag activation did not enhance the cytotoxic activity of MNC which did not respond to the antigen in the proliferation assay, and preincubation of these cells with IL-2 did not increase the activity. PPD stimulation enhanced the cytotoxic activity and induced strong proliferative responses in all MNC preparations. The role of NK cells in the protection against malaria is unknown, but they play a role in the protection against virus infection and in the immune surveillance against cancer. Our findings indicate that malaria antigens either directly or through the activation of immunoregulatory cells enhance the NK cell activity.
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PMID:Enhancement of human natural cytotoxicity by Plasmodium falciparum antigen activated lymphocytes. 244 9

Following previous studies of verapamil reversal of chloroquine resistance in malaria and multi-drug resistance in cancer cells, the effect of verapamil was investigated on nifurtimox-resistant Trypanosoma cruzi in vitro and antimony-resistant Leishmania donovani in vitro and in vivo. Verapamil alone was not active against either parasite, but in combination with nifurtimox it reversed the drug resistance of T. cruzi and in combination with sodium stibogluconate reversed the drug resistance of L. donovani.
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PMID:Reversal of drug resistance in Trypanosoma cruzi and Leishmania donovani by verapamil. 255 33

Ninety-nine consecutive patients who received cytotoxic therapy for acute leukemia were retrospectively studied to determine the pattern of infection at the Tata Memorial Hospital, Bombay, India. In all, 224 infective episodes occurred in these patients. Bacterial infection was the commonest type, accounting for 152 (67.9%) of 224 infective episodes, followed by fungal and viral infections (15.6% and 14.3%, respectively). Gram-negative organisms (Pseudomonas and Klebsiella) were the commonest bacterial organisms isolated, constituting 38 (76%) of 50 positive cultures; infection with Staphylococcus was rare (10%). Infective hepatitis, malaria, and systemic tuberculosis were responsible for fever with neutropenia in 20, 4, and 2 patients, respectively. Three hundred fifty-two patients with lymphoproliferative malignancies were also retrospectively studied to determine the pattern of infection. Only 53 infective episodes were recorded. In these patients, in contrast to those with acute leukemia, viral infection (33 [62.3%] of 53) and pulmonary tuberculosis (18 [34%] of 53) were frequently seen. It is interesting that 50% of our patients with hairy cell leukemia also had tuberculosis. Bacterial infection was conspicuous by its absence. Knowledge of the prevailing pattern of infection permits the development of investigative and therapeutic approaches of optimal efficacy.
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PMID:Pattern of infection in hematologic malignancies: an Indian experience. 260 80

The atoll community of Fenuafala was surveyed during July-August, 1987. A disproportionate demographic structure was found: There was a large, young population with an uneven sex distribution in the adolescent cohorts. Adoption of relatives was frequent. Employment varied according to sex, with women restricted from horticulture, fisheries, and hard labour. The use of alcohol and tobacco was common. Causes of mortality included cancer, heart failure, meningitis, alcoholism, and accidents. Bacterial and fungal skin infections were prevalent. There were several cases of congenital disorders. Malaria, leprosy, and most other tropical diseases were absent. However, there was a single case of filariasis. Musculoskeletal disorders were numerous and more common among women. Falls from trees have resulted in serious sequelae including epilepsy and death. Hypertension, diabetes, and gout appear to be on the increase, but angina and myocardial infarction were not reported. There were also cases of epilepsy and Parkinson's disease.
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PMID:Fenuafala health survey: the ecology of health and disease on a coral atoll village. 280 43


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